Литература / Европа+рекомендации+по+лечению+ССЗ+у+беременных+2018

ESC Guidelines

arrhythmias. Severe pulmonary regurgitation has been identified as an independent predictor of maternal complications, especially in patients with impaired RV function.

4.3.6.2 Obstetric and offspring risk

There is no evidence of increased obstetric risks.

4.3.6.3 Management

Mild and moderate PS are low-risk lesions (WHO risk classes I and II) and two or three follow-up sessions are sufficient. In patients with severe PS, monthly or bimonthly cardiac evaluations are advised, focusing on RV function. In severely symptomatic PS, which is unresponsive to medical therapy and bed rest, percutaneous valvuloplasty can be appropriate.

4.3.7 Congenital aortic stenosis

AS, aortic dilatation, and bicuspid aortic disease are discussed in sections 5 and 6.

4.3.8 Tetralogy of Fallot

4.3.8.1 Maternal risk

Women with repaired tetralogy of Fallot usually tolerate pregnancy well (WHO risk class II). Cardiac complications have been reported in 8% of repaired patients, especially in those taking cardiac medication prior to pregnancy.151 Arrhythmias and HF are the most common complications. Thrombo-embolism and endocarditis are rarer. Dysfunction of the RV and/or moderate to severe pulmonary regurgitation are risk factors. Previous pregnancy may be associated with a persisting increase in RV size and long-term cardiac events.

4.3.8.2 Obstetric and offspring risk

The risk of offspring complications is increased, in particular foetal growth restriction.152 Maternal screening for 22q11 deletion should be undertaken prior to pregnancy.

4.3.8.3 Management

Follow-up every trimester is sufficient in most patients. In women with severe pulmonary regurgitation, monthly or bimonthly cardiac evaluation is indicated. If RV failure occurs during pregnancy, treatment with diuretics should be started and bed rest advised. Early delivery or, rarely, transcatheter valve implantation could be considered in those who do not respond to conservative treatment.

4.3.9 Ebstein’s anomaly

4.3.9.1 Maternal risk

In women with uncomplicated Ebstein’s anomaly, pregnancy is often tolerated well (WHO risk class II). Symptomatic patients with cyanosis and/or HF should be counselled against pregnancy. The haemodynamic problems seen largely depend on the severity of tricuspid regurgitation (TR) and on RV function. Cyanosis (due to ASD/patent foramen ovale) and arrhythmias due to accessory pathways are common. There is also an increased risk of HF and pre-term delivery.153

4.3.9.2 Obstetric and offspring risk

Foetal and neonatal outcomes are related to maternal oxygen saturation and CO.

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4.3.9.3 Management

Even severe TR with HF can usually be managed medically during pregnancy. Women with interatrial shunting can develop progressive cyanosis during pregnancy and be at increased risk of paradoxical emboli, and these should be assessed at each visit.

4.3.10 Transposition of the great arteries

4.3.10.1 Maternal risk

In patients with transposition of the great arteries (TGA), the risks associated with pregnancy are mainly attributable to women with a previous atrial (Senning and Mustard) switch, not an arterial switch. Though many women with an atrial switch operation tolerate pregnancy relatively well, there is an increased risk of developing arrhythmias (sometimes life-threatening) and HF (WHO risk class III). An irreversible decline in RV function and worsening TR are also described.154,155 Patients with more than moderate impairment of RV function or greater than moderate TR should be advised against pregnancy.

4.3.10.2 Obstetric and offspring risk

The risk of low birth weight and pre-term delivery is 38%.

4.3.10.3 Management

Monthly or bimonthly review focusing on systemic RV function and arrhythmia is required. Diuretics and other HF therapies may be required.

4.3.10.4 Arterial switch operation

The risk of pregnancy seems low in these patients with good clinical condition pre-pregnancy and preserved ventricular function. Women with a dilated neo-aorta will require closer surveillance. Although this is now the most common operation for TGA, few data are available on pregnancy outcomes.

4.3.11 Congenitally corrected transposition of the great arteries

4.3.11.1 Maternal risk

In patients with congenitally corrected TGA (also called AV and ventriculoarterial discordance) risk depends on functional status, ventricular function, and the presence of arrhythmias and associated lesions (such as a VSD and pulmonary valve stenosis). Complications include arrhythmias and HF (WHO risk class III). These patients are also predisposed to developing AV block. Some 10% of patients have an irreversible decline in RV function.148,156 Patients in New York Heart Association (NYHA) classes III or IV, with ventricular dysfunction [ejection fraction (EF) <40%], or severe TR should be counselled against pregnancy.

4.3.11.2 Obstetric and offspring risk

The rate of foetal loss is increased, especially if there is cyanosis.

4.3.11.3 Management

For follow-up, it is recommended that patients have frequent echo surveillance of systemic RV function (every 4–8 weeks) and assessment of symptoms and rhythm.

3186

4.3.12 Fontan circulation

4.3.12.1 Maternal risk

Patients with a Fontan circulation have an increased risk of fertility issues, but successful pregnancy can occur. However, these are highto very high-risk pregnancies (WHO risk class III or IV). Atrial arrhythmias and NYHA class deterioration are not uncommon. Patients with saturations <85%, depressed ventricular function, moderate to severe AV regurgitation, refractory arrhythmia, or protein-losing enteropathy should be counselled against pregnancy (mWHO IV).

4.3.12.2. Obstetric and offspring risk

Fontan patients have a high-risk of miscarriage (30%).157 Antenatal and peripartum bleeding is common.158 There is an increased risk of premature birth, small for gestational age, and neonatal death.159

4.3.12.3 Management

It is recommended that Fontan patients have frequent surveillance during pregnancy (monthly) and in the first weeks after delivery. Fontan patients are at risk of thrombo-embolic complications and therapeutic anticoagulation should be considered (balanced with the risk of bleeding). Atrial arrhythmias should be treated promptly and this often requires electrical cardioversion.

4.4 Recommendations

Recommendations for pregnancy and pulmonary arterial hypertension

	Recommendations	Classa	Levelb
	Right heart catheterization is recommended
	to confirm the diagnosis of PAH (group 1).	I	C
	This can be performed during pregnancy
	but with very strict indications.10
	Treatment dose LMWH is recommended in
	pregnant patients with chronic thrombo-	I	C
	embolic pulmonary hypertension.
	If a PAH patient conceives on targeted PH
	therapies, consideration should be given to	IIa	C
	withdrawing embryotoxic drugs, taking into
	account the risks of withdrawal.
	In treatment-naive pregnant PAH patients,	IIa	C
	initiating treatment should be considered.23
	Pregnancy is not recommended in patients
	with PAH.119	III	B

LMWH = low molecular weight heparin; PAH = pulmonary arterial hypertension; PH = pulmonary hypertension.

aClass of recommendation. bLevel of evidence.

ESC Guidelines

Recommendations for congenital heart disease

Recommendations

Classa Levelb

Patients with a systemic right ventricle (Mustard/Senning or congenitally cor-

rected TGA), in NYHA class III/IV, systemic

IIa C

ventricular dysfunction (EF <40%), or severe TR should be advised against pregnancy.

Anticoagulation treatment should be con-

IIa C

sidered during pregnancy in Fontan patients.

Symptomatic patients with Ebstein’s anom-

aly with saturations <85% and/or heart failIIa C ure should be advised against pregnancy.

In patients with a Fontan circulation and saturations <85%, depressed ventricular func-

tion, moderate–severe AV regurgitation,

III C

refractory arrhythmia, or protein-losing enteropathy, pregnancy is not recommended.

AV = atrioventricular; EF = ejection fraction; NYHA = New York Heart Association; TGA = transposition of the great arteries; TR = tricuspid regurgitation.

aClass of recommendation. bLevel of evidence.

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.	5. Aortic diseases
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. Several heritable disorders affect the thoracic aorta, predisposing
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.	patients to both aneurysm formation and aortic dissection. These
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.	include		HTAD and		either	syndromic (Marfan				syndrome,
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.	Loeys–Dietz syndrome, osteoaneurysm syndrome, and vascular
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.	Ehlers–Danlos syndrome) or					non-syndromic HTAD				(i.e. only
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.	aortic aneurysm). New				genes	are regularly discovered. Other
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.	forms of congenital heart disease (e.g. tetralogy of Fallot and CoA)
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.	may also be accompanied by aortic dilatation, and finally non-
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.	heritable aortic pathology may occur.						160		Risk factors for aortic
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.	dilatation are hypertension and advanced maternal age. Pregnancy
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.	is a high-risk period for all patients with aortic pathology, which is
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.	rare during pregnancy				but associated			with very high mortal-
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.	ity.	161,162	Most deaths occur in women not previously known to
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.	have an aortopathy. Most of these women will have heritable dis-
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.	ease, so autopsy tissue should be saved for DNA analysis and fami-
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.	lies offered referrals for screening. Guidelines for the diagnosis
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.	and management of patients with thoracic aortic disease have
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.				163,164
.	been published.
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ESC Guidelines

5.1 Maternal and offspring risk

Haemodynamic and hormonal changes during pregnancy increase the susceptibility to dissection.165 Dissection occurs most often in the last trimester of pregnancy (50%) or the early post-partum period (33%). All women with a genetically proven syndrome or familial aortic pathology should have counselling on the risk of dissection and the recurrence risk, and have a complete evaluation including imaging of the entire aorta before pregnancy (see section 3). When assessing aortic diameters, body surface area should be considered, especially in women of small stature. Parity seems associated with increased aortic diameter.166 The effect of pregnancy on aortic dilatation is not clear.167,168 The diagnosis of aortic dissection should be considered in all patients with chest pain during pregnancy.

5.2 Specific syndromes

Marfan syndrome is thought to affect 1 in 5000 individuals. Although bicuspid aortic valve is more common (1–2% of the population), associated aortic complications are uncommon, accounting for only 6% of type A dissections during pregnancy.169

5.2.1 Marfan syndrome

The overall risk of a woman with Marfan syndrome having an aortic dissection associated with pregnancy is 3%.170 Aortic size is a major determinant of risk, but even women with an aortic root <40 mm have a risk of dissection of 1%.170,171 Although there are limited data, pregnancy should be avoided in Marfan patients with an aortic root diameter >45 mm as there is an increased risk of dissection. When the aorta is 40–45 mm, other factors should be considered, such as family history of dissection and rate of aortic growth.163 Distal aortic dissection and dissection of other vessels are also a risk. For this reason, even after successful aortic root replacement, patients remain at risk of further events.172 Studies focusing on the potential growth during pregnancy in Marfan patients demonstrated contradicting results; some demonstrated no significant growth, while others dem-

onstrated growth >3 mm with a partial diameter decrease post-

partum.167,168,173

Other important cardiac complications include progressive

mitral regurgitation (MR) due to mitral valve prolapse, new arrhythmia, and HF due to ventricular dysfunction.174,175

Obstetric complications are also increased, including premature rupture of membranes.19

5.2.2 Bicuspid aortic valve

Aortic dilatation occurs in <50% of patients with a bicuspid aortic valve and can occur even when valve function is normal. The dilatation can be in the distal ascending aorta, which cannot be adequately visualized by echocardiography. If not visible with echocardiography, MRI or CT should be performed pre-pregnancy. The risk of dissection is small. Risk factors are the type of bicuspid aortic valve

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3187

morphology, aortic dilatation, and CoA.176 Pregnancy should be avoided when the aorta diameter is >50 mm.

5.2.3 Vascular Ehlers–Danlos syndrome

Serious vascular complications occur almost exclusively in type IV Ehlers–Danlos syndrome (vascular). Maternal mortality is significant, and relates to uterine rupture and dissection of major arteries and veins. Pregnancy is therefore considered as a very high-risk undertaking and not advised.177 These women should be engaged in a shared decision-making process when contemplating pregnancy.

5.2.4 Turner syndrome

Turner syndrome is associated with an increased risk of congenital heart disease, aortic dilatation, hypertension, diabetes, and atherosclerotic events.178 Aortic dissection occurs rarely in Turner syndrome, but it is six times more common at younger ages than in the general population179 Risk factors for aortic dissection include aortic dilation, bicuspid aortic valve, and CoA.20,180 Pregnancy should be avoided when the aortic size index is >25 mm/m2. Also, after aortic root surgery, the patient remains at risk of type B dissection.

Spontaneous pregnancy can occur in mosaic Turner patients (0.5–10%), but pregnancy is now most commonly secondary to assisted fertility techniques. Cardiovascular evaluation is recommended before starting fertility treatment. Good BP control and diabetes management is mandatory for all Turner patients, especially during pregnancy.178

5.2.5 Other autosomal dominant aortopathies

With improved genotyping, a series of new aortopathies are being reported. These includes syndromic and non-syndromic HTAD. These conditions are considered high-risk, especially when the aorta is dilated, and may also have multisystem involvement with additional risks such as uterine rupture.181–184

5.3 Management

5.3.1 Follow-up and medical therapy

Depending on the aortic diameter, patients with aortic pathology should be monitored by echocardiography at regular intervals throughout the pregnancy and 6 months post-partum. In women with a highrisk of dissection or an already severely dilated aorta, monitoring every month is warranted, while in low-risk women with only a mildly dilated aorta, monitoring every 12 weeks seems reasonable. When needed, cardiac MRI without contrast can be used. Pregnancy should be supervised by a cardiologist and obstetrician who are alert to the possible complications. Strict BP control is advised, and antihypertensive treatment that is safe for the foetus should be initiated if necessary.185 In women with HTAD, beta-blocker therapy throughout pregnancy should be considered. In patients with Ehlers–Danlos syndrome type IV, celiprolol is recommended (also in normotensive women) because of the very high-risk of dissections and the benefit demonstrated in

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non-pregnant patients.186 Foetal growth should be monitored when the mother is taking beta-blockers.

5.3.2 Interventions

When progressive dilatation occurs during pregnancy, before the foetus is viable, surgical treatment with the foetus in utero should be considered. When the foetus is viable, caesarean delivery followed directly by aortic surgery is recommended (section 3). Caesarean section should be performed in a hospital in which cardiothoracic surgery and neonatal intensive care facilities are available.

In patients with acute aortic complications during pregnancy, management includes medical therapy where appropriate, and surgical or catheter-based interventions where needed.

Stanford type A aortic dissection occurring during pregnancy is a surgical emergency. Experienced cardiothoracic, cardiology, obstetric, and cardio-anaesthetic physicians must act rapidly to deliver the foetus (if viable) by caesarean section in a specialized cardiothoracic centre and proceed directly to repair of the dissection. If the baby is not viable, aortic surgery with the foetus in place should be performed. Although maternal outcome is good, foetal mortality is 20–30%.187

In the case of uncomplicated type B aortic dissection, conservative treatment with strict BP control using medication allowed during pregnancy is recommended.188

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ESC Guidelines

Thoracic endovascular aortic repair has recently been proposed as a new approach for complicated type B aortic dissection. Promising mid-term outcomes have been reported.189 However, the outcome

of thoracic endovascular aortic repair during pregnancy is only described in a few cases,190 and it is not recommended in the case of

genetic aortopathy.191–193

5.3.3 Delivery

The primary aim of intrapartum management in patients with ascending aorta enlargement is to reduce the cardiovascular stress of labour and delivery. If the woman is taking beta-blockers during pregnancy, they should be continued in the peripartum period.

If the ascending aorta diameter is 40–45 mm, vaginal delivery with expedited second-stage and regional anaesthesia should be considered to prevent BP peaks, which may induce dissection. Caesarean delivery may also be considered in these patients, based on the individual situation. Caesarean delivery should be considered when the aortic diameter exceeds 45 mm, and is recommended in patients with vascular Ehlers–Danlos syndrome type IV or acute or chronic aortic dissection.

Table 5 provides an overview of the specific aortic disease syndromes.

It is recommended that women with aortic disease have counselling about the risk of aortic dissection.19,178

Imaging of the entire aorta (CT/MRI) is recommended before pregnancy in patients with a genetically proven aortic syndrome or known aortic disease.53

In bicuspid aortic valve patients, imaging of the ascending aorta is recommended before pregnancy.

When a woman with known aortic dilatation (history of) dissection or genetic predisposition for dissection becomes pregnant, strict blood pressure control is recommended.185

Repeated echocardiographic imaging every 4–12 weeks (depending on diagnosis and severity of dilatation) is recommended during pregnancy and 6 months post-partum in patients with ascending aorta dilatation.194

For imaging of pregnant women with dilatation of the distal ascending aorta, aortic arch, or descending aorta, MRI (without gadolinium) is recommended.53

It is recommended to deliver all women with aortic dilatation or (history of) aortic dissection in an experienced centre with a pregnancy heart team, where cardiothoracic surgery is available.

In patients with an ascending aorta <40 mm, vaginal delivery is recommended.96

In patients with an ascending aorta >45 mm, caesarean delivery should be considered.

In patients with (history of) aortic dissection, caesarean delivery should be considered.

Prophylactic surgery should be considered during pregnancy if the aorta diameter is >45 mm and increasing rapidly.

When the foetus is viable, delivery before necessary surgery should be considered.96

In patients with an aorta 40–45 mm, vaginal delivery with epidural anaesthesia and an expedited second stage should be considered.

In patients with an aorta 40–45 mm, caesarean section may be considered.

Pregnancy is not recommended in patients with (or history of) aortic dissection.

When possible, the use of ergometrine is not recommended in women with aortic disease.

Specific syndromes

In patients with vascular Ehlers–Danlos syndrome, celiprolol is recommended.186

Beta-blocker therapy throughout pregnancy should be considered in women with Marfan syndrome and other heritable thoracic aortic diseases.

Pregnancy is not recommended in patients with severe dilatation of the aorta (heritable thoracic aortic disease such as Marfan syndrome >45 mm, bicuspid aortic valve >50 mm or >27 mm/m2 BSA, or Turner syndrome ASI >25 mm/m2 BSA).19,20

Pregnancy is not recommended in patients with vascular Ehlers–Danlos syndrome.26

ASI = aortic size index; BSA = body surface area; CT = computed tomography; MRI = magnetic resonance imaging. aClass of recommendation.

bLevel of evidence.

I	C
I	C
I	C
I	C
I	C
I	C
I	C
I	C
IIa	C
IIa	C
IIa	C
IIa	C
IIa	C
IIb	C
III	C
III	C
I	C
IIa	C
III	C
III	C

3190

6. Valvular heart disease

At childbearing age, valvular heart disease is often due to rheumatic heart disease, particularly in low–middle-income countries. Mechanical valve prostheses raise specific problems during pregnancy.92,195,196 Risk assessment and management need to consider the resources available in highand low–middle-income countries.

6.1 Stenotic valve lesions

In stenotic valve diseases, increased CO causes an increase in transvalvular gradient of 50%, mainly between the first and second

trimesters,197 which increases the risk of maternal and foetal complications.29,42,198

6.1.1 Mitral stenosis

6.1.1.1 Maternal risk

Mild mitral stenosis (MS) is generally well tolerated.198,199 HF occurs in one-third of pregnant women with a valve area <1.0 cm2

and in one-half of those with a valve area <1.5 cm2,199 most often during the second trimester, even in the absence of symptoms before pregnancy.198 Sustained AF, although rare (<10%), may precipitate HF and thrombo-embolic events.199,200 Mortality is between 0–3% in western countries198–200 and higher in low–mid- dle-income countries.201,202 NYHA class > II, systolic PAP >30 mmHg, severe stenosis, and older age are associated with maternal complications.199

6.1.1.2 Obstetric and offspring risk

The risk of acute HF peripartum depends on symptoms and PAP.194 Prematurity rates are 20–30%, intrauterine growth retardation 5–20%, and foetal death 1–5%.198–200,203 Offspring risk is higher in women in NYHA class III/IV during pregnancy.29,194

6.1.1.3 Management

Diagnosis. MS is considered clinically significant if valve area is <1.5

cm2.204,205 The reference measurement of MS severity is planimetry; Doppler-derived pressure half-time is less reliable but can be used during pregnancy.204,205 Mean gradient and PAP assess haemodynamic consequences and prognosis.204,205 The assessment of mitral anatomy and associated regurgitation is important when percutaneous mitral commissurotomy is considered.204,205 Before pregnancy, exercise testing is useful to assess objective exercise tolerance and exercise echocardiography may provide additional information.

Medical therapy. When symptoms or clinically significant PH (echocardiographically estimated systolic PAP >50 mmHg) develop, activity should be restricted and beta-1-selective blockers (preferably metoprolol or bisoprolol) commenced.5 Diuretics may be used if symptoms persist, avoiding high doses (see table ‘Recommendations for drug use in pregnancy’).5 Anticoagulation using UFH, LMWH, or vitamin K antagonist (VKA), according to the context and term, is recommended in the case of paroxysmal or permanent AF, left atrial thrombosis, or prior embolism.5 Anticoagulation should be considered in women in sinus rhythm with significant MS and spontaneous echocardiographic contrast in the left atrium, large left atrium (> 60 mL/m2), or congestive HF.

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ESC Guidelines

Interventions. All patients with significant MS should be counselled against pregnancy and intervention should be considered prepregnancy, favouring percutaneous intervention, even if asymptomatic, and even more so if the valve area is <1.0 cm2.198,204

During pregnancy, percutaneous mitral commissurotomy is preferably performed after 20 weeks of gestation. It should only be considered in women with NYHA class III/IV and/or systolic PAP >50 mmHg, despite optimal medical treatment in the absence of contraindications (see table ‘General Recommendations’).204 Closed commissurotomy remains an alternative in low–middle-income countries. Due to foetal risk, open-heart surgery should be reserved for cases in which all other measures have failed and the mother’s life is threatened.206

Follow-up during pregnancy. Clinical and echocardiographic follow-up is indicated monthly or bimonthly depending on haemodynamic tolerance. In mild MS, evaluation is recommended every trimester and prior to delivery.

Labour and delivery. Vaginal delivery should be favoured in patients with mild MS, and in patients with significant MS in NYHA class I/II without PH. Caesarean section is generally considered in patients who are in NYHA class III/IV or have PH, or in whom percutaneous mitral commissurotomy cannot be performed or has failed.

Follow-up and prognosis after delivery. Close monitoring is needed in the days following delivery. Late prognosis depends mainly on the risk of stenosis progression or re-stenosis after commissurotomy, and justifies regular follow-up.204

6.1.2 Valvular aortic stenosis

The main cause of AS is bicuspid aortic valve followed by rheumatic heart disease.

6.1.2.1 Maternal risk

Cardiac morbidity is related to the baseline severity of AS and symptoms.207 HF is rare (<10%) in women with moderate AS and in those who were asymptomatic before pregnancy, while it occurs in one out of four symptomatic patients.207 Even in patients with severe AS, pregnancy is often well tolerated if prior exercise tolerance was normal. Mortality is now rare if careful management is provided.194,198,207–209 Arrhythmias are rare.206 Women with bicuspid aortic valve have a low-risk of aortic dissection if the aortic diameter is <50 mm (section 5.2).

6.1.2.2 Obstetric and offspring risk

Obstetric complications may be increased in patients with severe AS.207,209 Pre-term birth, intrauterine growth retardation, and low birth weight occur in 20–25% of the offspring of mothers with moderate and severe AS, and are increased in severe AS.207 Miscarriages and foetal death rates are <5%. The risk of genetic transmission of LV outflow tract malformations justifies the performance of foetal echocardiography in AS due to bicuspid aortic valve.5

6.1.2.3 Management

Diagnosis. The severity of AS is assessed by combining flowdependent indices and valve area.204,205 Exercise testing is recommended in asymptomatic patients before pregnancy to evaluate

ESC Guidelines

exercise tolerance, BP response, and arrhythmias, and exercise echocardiography may provide additional information. In women with bicuspid aortic valve, aortic diameters should be assessed before and during pregnancy.

Medical therapy. Medical treatment and restricted activities are indicated if HF occurs during pregnancy. Diuretics can be administered for congestive symptoms.

Interventions. All symptomatic patients with severe AS or asymptomatic patients with impaired LV function or a pathological exercise test should be counselled against pregnancy, and surgery should be performed prepregnancy.10,204 Pregnancy should not be discouraged in asymptomatic patients, even with severe AS, when LV size and function and the exercise test are normal (see table ‘General Recommendations’). There should also be no recent progression of AS.

During pregnancy in patients who are severely symptomatic despite medical therapy, percutaneous valvuloplasty can be undertaken by an experienced operator.207 If this is not possible and patients have life-threatening symptoms, valve replacement should be considered after early delivery by caesarean section if this is an option (see table ‘General Recommendations’). Given the foetal risk of surgery, transcatheter aortic valve implantation is a promising alternative, but experience during pregnancy is very limited.

Follow-up during pregnancy. Regular follow-up is required by an experienced team. In severe AS, monthly or bimonthly cardiac evaluations including echocardiography are advised.

Labour and delivery. In severe symptomatic AS, caesarean delivery should be preferred. An individual approach is recommended for asymptomatic severe AS. In non-severe AS, vaginal delivery is favoured.

Follow-up and prognosis after delivery. Disease progression is frequent after delivery and requires close follow-up.204,208,210

6.2 Regurgitant lesions

6.2.1 Mitral and aortic regurgitation

Mitral and aortic regurgitation can be of rheumatic, congenital, or degenerative origin.92,199

6.2.1.1 Maternal risk

Women with severe regurgitation and symptoms or compromised LV function are at high-risk of HF.194,199 HF occurs in 20–25% of

women with moderate or severe rheumatic MR.199 Acute severe regurgitation is poorly tolerated. In women with congenital heart disease, significant left AV valve regurgitation is associated with cardiac complications during pregnancy. A persistent worsening of regurgitation may occur.42

6.2.1.2 Obstetric and offspring risk

No increased risk of obstetric complications has been reported. Intrauterine growth retardation occurs in 5–10%, and other

offspring complications in <5%, of women with moderate or severe MR.199

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3191

6.2.1.3 Management

Diagnosis. Evaluation, preferably pre-conception, should include the assessment of symptoms and comprehensive echocardiographic evaluation of regurgitation severity, LV dimensions, and function.204

Ascending aortic diameters should be measured in women with aortic regurgitation, especially in those with bicuspid valves.

Medical therapy. Symptoms of fluid overload can usually be managed medically.

Interventions. Pre-pregnancy surgery favouring valve repair should be performed according to guidelines.204

In acute severe regurgitation with therapy-refractory HF, surgery is sometimes unavoidable during pregnancy. If the foetus is sufficiently mature, delivery should be undertaken prior to cardiac surgery (see table ‘General Recommendations’).

Follow-up during pregnancy. Follow-up is required every trimester in mild/moderate regurgitation, and more often in severe regurgitation.

Labour and delivery. Vaginal delivery with epidural anaesthesia and shortened second stage is advisable.

Follow-up and prognosis after delivery. The prognosis depends on the regurgitation severity and its consequences on symptoms, LV size, and function.

6.2.2 Tricuspid regurgitation

Secondary TR is more frequent than primary TR, which may be due to endocarditis or Ebstein’s anomaly.

Maternal risk is usually determined by left-sided valve disease or PH. However, maternal risk can be increased in severe symptomatic TR or in women with RV dysfunction.50 In women with congenital heart disease, moderate/severe AV valve regurgitation may be associated with maternal cardiac complications, which are mainly arrhythmias.42

Even severe TR with HF can usually be managed conservatively during pregnancy (see table ‘General Recommendations’). When surgery is necessary for left-sided valve lesions, additional tricuspid repair is indicated in severe TR and should be considered in moderate TR with annular dilatation (> 40 mm).204 In severe symptomatic TR, repair should be considered pre-pregnancy.

6.3 Atrial fibrillation in native heart valve disease

A high thrombo-embolic risk is associated with AF, particularly in clinically significant MS. Immediate anticoagulation is required, using LMWH at therapeutic doses in the first and last trimesters, and VKAs with the usual target INRs or LMWH for the second trimester. NonVKA OACs are contraindicated throughout pregnancy. The choice between cardioversion and rate control using digoxin or betablockers depends on the severity of the underlying valve disease and the tolerance (see section 12).

6.4 Prosthetic valves

6.4.1 Choice of valve prosthesis

When implantation of a prosthetic valve is unavoidable in a woman who wants to become pregnant in the future, valve selection is

3192

challenging. Mechanical valves offer excellent haemodynamic performance and long-term durability, but the need for anticoagulation increases maternal and foetal mortality and morbidity, and the risk of major cardiac events during pregnancy is much higher than with bioprosthetic valves.196,211,212 However, bioprosthetic valves in young women are associated with a high-risk of structural valve deterioration resulting in the risk of going through pregnancy with a dysfunctional valve, and eventually in the inevitable need for re-operation. Transcatheter valve implantation (currently especially in pulmonary valves) and the Ross procedure in aortic valve disease (pulmonary autograft in the aortic position and pulmonary homograft) are alternative options to be considered.5 Data on pregnancy after a Ross procedure are scarce but indicate low-risk in the absence of aortic dilatation.213 A desire for pregnancy is a class IIa indication for a biological valve.204 In young women who wish to become pregnant in the future, the pregnancy heart team should be involved in the choice of a specific prosthesis. The final choice should be made after extensive sharing of information and discussion with the patient.

6.4.2 Pregnancy risk with bioprostheses

The risk of maternal cardiovascular complications in women with a bioprosthesis is low in those with no or minimal bioprosthesis dysfunction and uncompromised ventricular function. When significant bioprosthesis dysfunction is present, the risk of complications can be significant. Pre-pregnancy assessment and counselling, as well as follow-up, medical treatment, and indications for intervention, are comparable with those for pregnancies with native valve dysfunction.

6.5 Mechanical prostheses and anticoagulation

In women with mechanical valves, pregnancy is associated with a very high-risk of complications (WHO risk classification III). In the ROPAC registry, the chances of an event-free pregnancy with a live birth were 58% for women with a mechanical valve, compared with 79% for women with a bioprosthesis and 78% for women with heart disease but no valve prosthesis.196 A recent study from the UK reported a favourable outcome for mother and baby in only 28% of cases.214 The main risks are related to the need for anticoagulation therapy (valve thrombosis and haemorrhagic complications). Additional risks are related to ventricular and valvular dysfunction.

6.5.1 Maternal risk

The risk of valve thrombosis is markedly increased during pregnancy. The risk is lower with adequate dosing of anticoagulant therapy, and depends on the type and position of the mechanical valve, and on additional patient-related risk factors.204 In the ROPAC registry, valve thrombosis occurred in 4.7% of 202 pregnancies and mortality was 20%.196 In the UK study, maternal mortality related to thrombotic complications or valve dysfunction occurred in 9% and severe morbidity in 41% (16% thrombo-embolic complications).214 The risk of valve thrombosis is relatively low with VKAs throughout pregnancy (0–4%).196,215–219 Scarce evidence concerning UFH in the first trimester or throughout pregnancy indicates a high-risk of valve thrombosis (9–33%); additional risks are thrombocytopenia and osteoporosis.215,218,219 LMWH is also associated with the risk of valve thrombosis.196,214,215,219–222 Because the dose requirement

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ESC Guidelines

markedly increases due to increased renal clearance, monitoring of anti-Xa levels with dose adjustment decreases the risk. LMWH throughout pregnancy with anti-Xa monitoring and dose adjustment according to peak levels carries a valve thrombosis risk of 4.4–8.7%.219,223 Suboptimal target anti-Xa levels or poor compliance often contribute to valve thrombosis, but several valve thromboses occured with peak anti-Xa levels within the target range of 1.0–1.2 IU/mL.221,222 Valve thrombosis occurs in 5.8–7.4% when LMWH is used in the first trimester only, which is similar to using LMWH throughout pregnancy.196,215,219,223 However, the high-risk of valve thrombosis in the UK study was mainly related to the use of LMWH throughout pregnancy. The occurrence of valve thrombosis with adequate peak anti-Xa levels has raised concerns about the safety of this approach. Fast renal clearance can result in subtherapeutic trough (pre-dose) anti-Xa levels despite adequate peak levels, but data on pregnancies with LMWH dosing according to trough and peak anti-Xa levels are limited to case reports.5,224–226 In conclusion, there are unresolved questions concerning LMWH in pregnant women with mechanical valves, including optimal anti-Xa levels, the importance of peak vs. trough levels, the best time intervals for antiXa monitoring, and the duration of use.

Current evidence (lacking adequate randomized studies) indicates that the use of VKAs throughout pregnancy, under strict INR control, is the safest regimen to prevent valve thrombosis.196,215–219 LMWH is possibly superior to UFH for preventing valve thrombosis.196,219,223

6.5.2 Obstetric and offspring risk

All anticoagulation regimens carry an increased risk of miscarriage and haemorrhagic complications, including post-partum haemorrhage and retroplacental bleeding leading to premature birth and foetal death.196,216,218,220,221 ROPAC shows that VKAs during the first trimester are associated with an increased risk of miscarriage compared with LMWH or UFH (28.6% vs. 9.2%), and the live birth rate is lower, in line with other literature.196 Two systematic reviews concluded that the risk of foetal loss is dose-related (foetal loss rate with low-dose VKA is 13.4–19.2%, total foetal loss rate with VKA is 32.5%). Foetal loss rate with a combined heparin/VKA regimen is 22.7%,and with LMWH throughout pregnancy is 12.2%.217,219 Comparison between studies is hampered by reporting differences,

and conclusions concerning the safety of low-dose VKA are controversial.5,196,217,219,223,227 VKA use in the first trimester results in embryopathy (limb defects, nasal hypoplasia) in 0.6–10% of cases.216,218,219,228 UFH and LMWH do not cross the placenta, therefore substitution of VKA with UFH or LMWH in weeks 6–12 almost eliminates the risk of embryopathy. The embryopathy risk is also dose-dependent (0.45–0.9% with low-dose warfarin).217,219 Additionally, there is 0.7–2% risk of foetopathy (e.g. ocular and central nervous system abnormalities, intracranial haemorrhage) with VKAs in the second and third trimester.216,219,223,228–230 Foetopathy has been described with UFH but not with LMWH throughout pregnancy.219,223 Vaginal delivery while the mother is on VKAs is contraindicated because of the risk of foetal intracranial bleeding.228 Haemorrhagic complications in the mother occur with all regimens, but the incidence is lower with VKA throughout pregnancy than with LMWH/UFH throughout pregnancy.219 Addition of low-dose aspirin to VKA or heparin has no proven advantage in preventing valve

ESC Guidelines

thrombosis but is associated with significantly more maternal bleeding complications, including fatal events.196,219,222

6.5.3 Management

Pre-pregnancy evaluation should include the assessment of symptoms and echocardiographic evaluation of ventricular function, as well as prosthetic and native valve function. The type and position of valve(s), as well as the history of valve thrombosis, should be taken into account. The option to avoid pregnancy should be discussed with the mother.

6.5.3.1 Medical therapy

The advantages and disadvantages of different anticoagulation regimen should be discussed extensively before pregnancy. The mother must understand that the use of VKAs is the most effective regimen to prevent valve thrombosis, and therefore the safest regimen for her, and that risks to the mother also jeopardize the baby. However, the increased risks of embryopathy, foetopathy, foetal loss, and foetal haemorrhage associated with the use of VKAs need to be discussed while considering the VKA dose. The higher risk of valve thrombosis and lower foetal risks associated with LMWH should be discussed. Compliance with prior

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3193

anticoagulant therapy should be considered. The mother should understand that whatever anticoagulation regime is chosen, her strict compliance is crucial for a successful outcome of the pregnancy.

VKAs should be continued until pregnancy is achieved. Continuation of VKAs throughout pregnancy should be considered when the VKA dose is low (see Table 7). Because of the low risks of embryopathy, foetopathy (<2%), and foetal loss (<20%), VKAs are the most effective regimen to prevent valve thrombosis.215,218,219 The target INR should be chosen according to current guidelines,204 with INR monitoring weekly or every 2 weeks. Self-monitoring of INR in suitable patients is recommended. Alternatively, a switch to LMWH from weeks 6–12 under strict monitoring may be considered in patients with a low dose requirement, after full information has been given to the mother. When a higher dose of VKAs is required, discontinuation of VKAs between weeks 6 and 12, and replacement with adjusted-dose i.v. UFH or LMWH twice daily with dose adjustment according to peak anti-Xa levels, should be considered. See table ‘Recommendations for the management of prosthetic heart valves’ and Figures 2–4 for details of dosing and monitoring. Alternatively, continuation of VKAs may be considered in these patients after fully informed consent. In addition to monitoring

peak anti-Xa levels, monitoring of the trough (pre-dose) anti-Xa level and dose-adjustment to maintain this trough level at >0.6 IU/mL may be considered based on theoretical grounds, despite limited evidence.5,224,225 The starting dose for LMWH is 1 mg/kg body weight for enoxaparin and 100 IU/kg for dalteparin, twice daily subcutaneously. The dose should be adjusted daily according to peak (or peak and trough) anti-Xa levels and weekly when the target anti-Xa level is achieved.5,224,225 The routine addition of acetylsalicylic acid is not recommended.196,219,222 When UFH is used, after a stable aPTT has been achieved, UFH should be monitored weekly using aPTT, with a prolongation of >2 times the control. During the second and third trimester, VKAs are the favoured therapy. For details on management see Figures 2–4.

6.5.3.2 Surveillance during pregnancy

These high-risk pregnancies should be managed by a pregnancy heart team in an expert centre. The effectiveness of the anticoagulation regimen should be monitored weekly or every 2 weeks depending on the anticoagulation regimen (see Table 7), and clinical follow-up including echocardiography should be performed monthly.

Figure 4 Flowchart on anticoagulation in mechanical valves and target international normalized ratio for mechanical prostheses (modified from Baumgartner et al.204). INR = international normalized ratio; LVEF = left ventricular ejection fraction. aMitral or tricuspid valve replacement, previous thrombo-embolism, atrial fibrillation, mitral stenosis of any degree, or LVEF <35%. bCarbomedics, Medtronic Hall, ATS, or Medtronic Open-Pivot, St Jude Medical, On-X, or Sorin Bicarbon. cOther bileaflet valves with insufficient data. dLillehei-Kaster, Omniscience, Starr-Edwards (ball-cage), Bjo¨rkShiley and other tilting-disc valves; any pulmonary valve prosthesis.